Knockdown of SMARCA4 leads to ferroptosis of HT1080 cells through inhibition of cholesterol synthesis / 中国病理生理杂志

AIM:To investigate the role and molecular mechanisms of SMARCA4(SWI/SNF-related,matrix-associated,actin-dependent regulator of chromatin,subfamily A,member 4)in ferroptosis.METHODS:(1)Human fi-brosarcoma HT1080 cells were treated with dimethyl sulfoxide(DMSO)and different concentrations(31.25,62.5 and 125 nmol/L)of Ras-selective lethal small molecule 3(RSL3;ferroptosis inducer).Each treatment had 3 replicate wells of cells.The protein levels of SMARCA4 were detected by Western blot.(2)Two small interfering RNAs(siSMARCA4-1 and siSMARCA4-2)were constructed according to the SMARCA4 gene sequence.After SMARCA4 knockdown,each treat-ment had 3 replicate wells of cells,and the protein levels of SMARCA4 were determined by Western blot.Effects of DMSO,necrostatin 2 racemate(Nec-1s;necroptosis inhibitor),Z-VAD(OMe)-FMK(Z-VAD,pan-caspase inhibitor/apoptosis inhibitor)and ferrostatin-1(Fer-1,ferroptosis inhibitor)on cell viability were assessed using high-content analy-sis.The levels of ferroptosis indicators,including prostaglandin-endoperoxide synthase 2(PTGS2)transcription,lipid peroxidation,reactive oxygen species(ROS),labile iron pool(LIP)and glutathione,were determined by RT-qPCR and flow cytometry.The mRNA expression levels of pivotal iron metabolism genes,ferroptosis-related ROS regulatory genes,and cholesterol synthesis-related genes were measured using RT-qPCR.Impact of cholesterol on the cell viability were as-sessed using high-content analysis.(3)Common differential gene analysis and gene ontology(GO)enrichment analysis were performed on published online data.RESULTS:(1)Treatment with RSL3 significantly reduced the protein level of SMARCA4(P＜0.05).(2)Knockdown of SMARCA4 resulted in ferroptosis.(3)Knockdown of SMARCA4 did not induce ferroptosis by modulating the LIP and the transcription levels of ROS-related genes.(4)Knockdown of SMARCA4 affected the pathways associated with the cell membrane,lipid raft,and cholesterol synthesis.(5)Addition of cholesterol to cell culture medium rescued the ferroptosis induced by SMARCA4 knockdown(P＜0.01).CONCLUSION:Treatment with RSL3 reduces the protein level of SMARCA4 in human fibrosarcoma HT1080 cells,and inhibition of cholesterol synthesis by SMARCA4 knockdown leads to the ferroptosis of HT1080 cells.

Exploring the Effect of Medication-Containing Serum of Pingwei Capsules （平胃胶囊） on MNNG-Induced Inflammatory Cancer Transformation of Human Gastric Mucosal Epithelial Cells Based on Raf/MEK/ERK Pathway / 中医杂志

ObjectiveTo explore the possible mechanism of Pingwei Capsules （平胃胶囊） for chronic atrophic gastritis from rapidly accelerated fibrosarcoma / mitogen-activated protein kinase /extracellular-signal-regulated kinase （Raf/MEK/ERK） pathway that influences the activation of fibrosarcoma protein/mitogen. MethodsFifteen SD rats were randomly divided into 5 rats in the blank group and 10 rats in Pingwei Capsules group. The rats in the blank group were given 1 ml/100 g of saline by gavage， and the rats in Pingwei Capsules group were given 0.63 g/（kg·d） of Pingwei Capsule suspension by gavage， and serum was collected for 3 consecutive days. N-methyl-N'-nitro-N-nitrosoguanidine （MNNG） was used to induce human gastric mucosal epithelial cells GES-1 to establish a precancerous lesion cell model. The successful cells were divided into control group （10% fetal bovine serum）， blank serum group （10% fetal bovine serum plus 10% blank serum）， and medication-containing serum group （serum with medication of Pingwei Capsule）， and the volume fraction and time of intervention of Pingwei Capsule-containing serum were screened by CCK-8 assay. Human gastric mucosal epithelial cells GES-1 were divided into normal group， model group， blank serum group， medication-containing serum group， U0126 group， and combined group， with 6 replicate wells in each group. After successful modelling of the cells in all groups except the blank group， an equal volume of fetal bovine serum was added to the normal and model groups， an equal volume of blank serum was added to the blank serum group， a screening volume fraction of Pingwei Capsule-containing serum was added to Pingwei Capsule group， a 10 μmol/L mitogen-activated extracellular signal regulated kinase 1 （MEK1） inhibitor U0126 was administered in the U0126 group， an equal dose of Pingwei Capsule-containing serum plus 10 μmol/L of U0126 was administered to the combined group. After the selected incubation time， the level of interleukin 6 （IL-6） was detected in the cells by ELISA， the expression of IL-6 and MEK1 was detected by immunofluorescence， and the expression of IL-6， Raf， MEK1， and ERK mRNA was detected by RT-qPCR， and the expression of IL-6， Raf， MEK1， and ERK mRNA in the cells was detected by Western blot. ResultsThe 5.35% volume fraction， 48 h intervention of Pingwei Capsule-containing serum was selected for subsequent experiments. Compared with the normal group， the IL-6 content in cell supernatants and the expression of IL-6， Raf， MEK1， ERK mRNA and ERK1/2 proteins in cells increased in the model group and blank serum group （P＜0.01）. Compared with the model group， all of the above indexes were improved in medication-containing serum group， U0126 group， and combined group （P＜0.05 or P＜0.01）. Compared with medication-containing serum group， the expression of IL-6， MEK1 expression， the expression of IL-6， Raf， MEK1 and ERK mRNA， and the expression of IL-6， Raf， MEK1 and ERK1/2 proteins reduced in the cells of combined group （P＜0.05 or P＜0.01）. Compared with the U0126 group， IL-6 expression reduced and IL-6， MEK1 and ERK1/2 protein expression reduced in cells of combined group （P＜0.05 or P＜0.01）. ConclusionThe Pingwei Capsule-containing serum may play a role in the treatment of chronic atrophic gastritis by improving the inflammation-cancer transformation of GES-1 cells through inhibiting the Raf/MEK/ERK pathway.

Hei Xiaoyaosan Regulates RAS/RAF/MEK/ERK Signaling Pathway to Ameliorate Oxidative Stress in Rat Model of AD / 中国实验方剂学杂志

ObjectiveTo investigate the role and mechanism of Hei Xiaoyaosan in intervening in oxidative stress in the rat model of Alzheimer's disease （AD） via modulating the rat sarcoma （RAS）/rapidly accelerating fibrosarcoma （RAF）/mitogen-activated protein kinase kinase （MEK）/extracellular signal-regulated kinase （ERK） signaling pathway. MethodOne hundred 4-month-old SPF-grade Wistar male rats were randomly grouped as follows： 10 in the blank group， 10 in the sham group （bilateral hippocampus injected with 1 μL normal saline）， and 80 in the modeling group ［bilateral hippocampus injected with 1 μL amyloid beta protein 1-42 （Aβ1-42） solution for the modeling of AD］. Fifty rats qualified for modeling were selected and randomized into the model， donepezil hydrochloride （0.5 mg·kg-1）， and high-， medium-， and low-dose （15.30， 7.65， 3.82 g·kg-1， respectively） Hei Xiaoyaosan groups. The rats were administrated with corresponding drugs by gavage once a day for 42 consecutive days. At the end of gavage， Morris water maze test was performed to examine the learning and memory abilities of the rats， and Nissl staining was used to observe the pathological changes of neurons in CA3 region of the hippocampus. The immunofluorescence assay was used to observe Aβ deposition and tau phosphorylation. Western blot was employed to determine the protein levels of RAS， RAF， phosphorylated （p）-RAF， MEK， p-MEK， ERK， and p-ERK in the hippocampal tissue. Biochemical methods were used to determine the levels of reactive oxygen species （ROS）， malondialdehyde （MDA）， and superoxide dismutase （SOD） in the hippocampal tissue. ResultCompared with the sham group， the model group showed prolonged escape latency （P<0.01）， shortened swimming distance in the target quadrant （P<0.01）， reduced and uneven stained Nissl bodies， enhanced fluorescence intensity of Aβ and p-tau （P<0.01）， up-regulated protein levels of RAS， p-RAF， p-MEK， and p-ERK in the hippocampal tissue （P<0.01）， increased ROS and MDA content （P<0.01）， and decreased SOD activity （P<0.01） on day 5. Compared with the model group， donepezil hydrochloride and high-， medium-， and low-dose Hei Xiaoyaosan shortened the escape latency （P<0.01）， increased the swimming distance in the target quadrant （P<0.01）， improved the arrangement， morphology， and structures of neurons and the number and distribution of Nissl bodies， decreased the fluorescence intensity of Aβ and p-tau （P<0.01）， up-regulated the protein levels of RAS， p-RAF， p-MEK， and p-ERK （P<0.05， P<0.01）， decreased the ROS and MDA content （P<0.01）， and increased the SOD activity （P<0.01） on day 5. ConclusionHei Xiaoyaosan may ameliorate oxidative stress， reduce Aβ and p-tau levels， and inhibit hippocampal neuronal damage by regulating the RAS/RAF/MEK/ERK signaling pathway， thus improving learning and memory abilities.

Development of radiolabeled tetramer that targeting fibroblast activation protein and theranostic research in tumor xenografts / 中华核医学与分子影像杂志

Objective:To develop a tetramer probe targeting fibroblast activation protein (FAP), named 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-4P(FAP inhibitor (FAPI)) 4, evaluate its biodistribution and PET image in FAP-positive-tumor bearing nude mice, and explore its feasibility as a novel radio-regent for treatment of FAP-positive tumor. Methods:FAP tetramer probe was constructed on the FAPI-46 motif with four mini-polyethylene glycol (PEG)(PEG 3) spacers between the four FAPI motifs, denoted as 4P(FAPI) 4. DOTA was used as the chelator for radiolabeling with 68Ga and 177Lu. The FAP binding characteristics were test by in vitro cell competitive binding experiment. Small-animal PET, in vivo biodistribution, and radionuclide targeting therapy were performed in HT-1080-FAP tumor bearing nude mice ( n=39). Independent-sample t test was performed to analyze tumor uptake data, and two-factor repeated measures analysis of variance was utilized to compare tumor volume data in radioactive isotope therapy. Results:Cell experiment showed that FAPI-tetramer and FAPI-monomer had similar half maximal inhibitory concentration values (3.29 and 2.15 nmol/L). 68Ga/ 177Lu radiolabeled FAPI-tetramer had better tumor uptake and retention than FAPI-monomer in small-animal PET and in vivo biodistribution experiment, with the tumor uptake for 177Lu-DOTA-4P(FAPI) 4 and 177Lu-FAPI-46 at 48 h of (18.72±1.32) vs (2.72±1.20) percentage activity of injection dose per gram of tissue (%ID/g) ( t=15.55, P<0.001). 177Lu-DOTA-4P(FAPI) 4 group showed best anti-tumor efficacy compared with 177Lu-FAPI-46 and control group in radionuclide targeting therapy. On the 2nd day after the start of treatment, the tumor volume in the tetramer treatment group was significantly smaller than that in the control group (mean difference 67.19 mm 3, P=0.049); on the 14th day after the start of treatment, the tumor volume in the tetramer treatment group was significantly smaller than that in the monomer treatment group (mean difference 414.33 mm 3, P=0.005). Conclusion:FAPI-tetramer can improve tumor uptake and retention ability compared with FAPI-46, and 177Lu-DOTA-4P(FAPI) 4 can be a promising radio-agent for FAP-positive tumor therapy.

Feline Injection-Site Sarcoma Complete Remission After Treatment with Isopathic medicine: a case repor

Feline injection-site sarcomas (FISS) were described for the first time in 1991. They are neoplasms of mesenchymal origin that appear in body regions routinely used for the application of vaccines or other injections [1]. Those are very aggressive tumours that relapse and have a high rate of mortality. The tumour can appear between 3 months and 3 years after the injection, but in some cases, it can happen after 15 years of the vaccineor otherinjections. Isopathy is one approach of homeopathy, in which the biological agent thatcausesa disease are prepared in high dilution to treat the same disease. This case report is about a 13-year-old mix breed spay cat. In September 2019 it received the vaccine Rabsin® (Boehringer Ingelheim) and 4 months later the owner noticed a lump at the injection area. One year later (September 2020) the lump start growing rapidly and on January 12th, 2021,started the appointments.The other veterinarians recommend euthanasia since the tumour was very bigand the catwasnot mild, was losing weightand appetite. The owner wanted to try another treatment before euthanasia since the cat was still active, interacting with the other cat and the people at the house.The lump was located on her back, in the end of the right ribcage, and it was around 7cm of diameter. It wasfirmandattachedto the muscles. AnIsopathy medicine with the same vaccinewas prepared, being the isotherapic 12CH administered 5 drops BID.Beside the isopathyvitaminsof Bcomplex and Omega 3were prescribed.The cat was seen every15 days andcontact telephonically was kept as well. The treatment started on January 19th, 2021. On January 21st, 2021,all the tumour was ulcerated and looser. On February 2nd,2021 the potencywas changedto 14CH, 5 drops, BID. On February 4ththe tumour felt away and was sent for histopathological study. On February 20th, 2021,the result described it as a Fibrosarcoma grade II. The ulcer that appeared after the tumour felt away became a big wound and the ownerstarted cleaning itwith propolis and lavender oleateeveryday anditwas controlledonce a week. OnMarch31st, 2021,the catwas eating well,strong, not mild,didnot allowedit to be cleaned. The woundseems to be more superficial,largerand it appears thata small lump was growing again.Isotherapic 15CH, 5 drops once a weekwas indicated.On April4th, 2021,the cat waseating well, good general conditionand the small lump that was growing wasshrinkingand the wound becoming more superficial. OnApril 9th,2021the cat seems painful, not eating well, constipated. Isopathy was suspended and started with Meloxican0,1mg/kg SID for 3 days.Was indicatedNatrum muriaticum30CH, 5 drops every hour, total 3 treatments and then once a day. On April 13th, 2021,the cat was better, defecate. But since April 9ththe cat could never be stable again. It has ups and downs and was treated withdifferent homeopathic remedies (Natrum muriaticum30Ch, Silicea200CHand Silicea1000CH, Staphisagria 200CH)until June 8th, 2021,when it was euthanised.No necropsy was done. The question was,what happenedwith the catsince itwas getting better?The following aphorisms could explain it:§156 "...The restoration, however, leads to the goal of the cure, if it is not preventedby strange medicinal influence, by errors in the lifestyle or by passions." And§10"With no vital powerthe material organism is not capable of any sensation, function or self-preservation..."[2].The informed consent formwas obtained from the owner of the cat.

CT features of primary hepatic fibrosarcoma / 中华消化外科杂志

Objective:To investigate the computed tomography (CT) features of primary hepatic fibrosarcoma (PHF).Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 8 patients with PHF who were admitted to 2 medical centers from January 2010 to December 2019, including 3 cases of Yueqing People's Hospital of Zhejiang and 5 cases of Wenzhou People's Hospital of Zhejiang were collected. There were 5 males and 3 females, aged 50 years(range, 39?60 years). All patients underwent abdominal CT plain and enhanced examination, and surgical procedures were selected based on patients' will and individual situations. Surgical tumor specimens were given pathological examination and immunohistochemical staining. Observation indicators: (1) imaging features of CT examination; (2) treatment and pathological examinations; (3) follow-up. Follow-up was performed by outpatient examination or hospitalization to detect survival of patients and tumor recurrence up to December 2020. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers. Results:(1) Imaging features of CT examination: 8 patients received preoperative CT examinations, 3 cases of which were diagnosed as malignancies, 3 cases were diagnosed as hepatic space-occupying lesions, 2 cases were diagnosed as intrahepatic cholangiocarcinoma. ① Tumor location and general status: 8 patients had single tumor, of which 6 cases had tumor located in the right lobe of the liver and 2 cases had tumor located in the left lobe of the liver. The tumor was in oval shape in 5 patients and in circular in 3 patients. The maximum diameter of tumor in 8 patients was 9.3 cm(range, 4.0?15.0 cm). There were 1 case with tumor maximum diameter ≤5.0 cm, 4 cases with tumor maximum diameter as 5.1?10.0 cm, 3 cases with tumor maximum diameter >10.0 cm. ② CT plain scan showed uniform low density in 2 cases and uneven low density in 6 cases and the CT value of 8 cases was 40 HU(range, 29?43 HU). The tumor showed expansive growth with clear boundary in 6 cases, and invasive growth with unclear boundary in 2 cases. Five cases had intratumoral necrosis and cystic transformation, 2 cases had intratumoral strip hemorrhage, and 1 case of intratumoral calcification. There was 1 case with hilar lymph node metastasis. ③ Enhanced CT scan showed 8 cases with uneven enhancement in arterial phase, 8 cases with uneven tumor density in portal vein phase, 8 cases with intratumoral enhancement slowly withdrew in delayed phase and the density lower than liver parenchyma. (2) Treatment and pathological examinations: ① 8 patients under-went surgical resection, without intrahepatic or hilar metastasis. ② The results of postoperative pathological examination showed 2 cases with grade Ⅰ tumor differentiation (low potential malignancy), 5 cases with grade Ⅱ and Ⅲ tumor differentiation (moderate potential malignancy), 1 case with grade Ⅳ tumor differentiation (high potential malignancy). ③ Immuno-histochemical staining showed that 8 cases were positive for vimentin, CD10, p53 and negative for smooth muscle actin, keratin19, epithelial membrane antigen, endotheliocyte 34. All 8 patients were diagnosed as PHF. (3) Follow-up: all 8 patients were followed up for 7 to 128 months, with a median follow-up time of 53 months. The overall survival time of 8 patients was 15 to 122 months, and the median overall survival time was 45 months. One patient died of tumor recurrence and distant metastasis at 17 months after surgery, and the survival time of 7 patients was >28 months.Conclusions:CT plain scan of PHF showed uneven low-density masses. After enhancement, the arterial phase shows the tumor ring or peripheral nodular uneven enhancement, the intratumoral strip-shaped enhanced blood vessels. The portal vein phase shows the tumor-like small patches or grid-like continuous enhancement. The delayed phase is characterized by the slow withdrawal of intratumoral enhancement.

Research progress on MAFB gene polymorphism and nonsyndromic cleft lip and palate / 口腔疾病防治

@#Nonsyndromic cleft lip with/without cleft palate is a common congenital birth defect of the maxillofacial region. The pathogenic mechanism is related to the interaction of genes and environmental factors. At present, there are many studies on genes, and genome-wide association analysis has found that the new susceptibility gene v-maf musculoaponeurotic fibrosarcoma oncogene homolog B (MAFB) is associated with the development of nonsyndromic cleft lip with/without cleft palate. This paper reviews the research progress on the correlation between single nucletide polymorphism(SNPs) in MAFB and nonsyndromic cleft lip with/without cleft palate. The results of this review reveal how the MAFB gene is expressed and differentiated in various cell types and plays an important role in maintaining the development of various organs, such as the brain, pancreas, and parathyroid glands. The MAFB gene is significantly associated with the occurrence of nonsyndromic cleft lip with/without cleft palate in the Asian population. rs13041247, rs11696257, rs17820943 and other teratopoietic single nucleotide loci are the most commonly studied teratopoietic single nucleotide loci, and the research conclusions on the correlation between SNPs in MAFB genes are obviously different in different populations. The interaction between the MAFB gene and other susceptibility genes leads to the occurrence of nonsyndromic cleft lip with/without cleft palate; nevertheless, more in-depth research is needed on specific mechanisms and approaches based on the relationship between these two factors.

Infantile fibrosarcoma: 16 case reports / 中华实用儿科临床杂志

Objective:To summarize the clinical characteristics of infantile fibrosarcoma(IFS) and analyze the high risk factors that affect IFS prognosis.Methods:Totally, 16 patients were diagnosed IFS in Department of Pedia-trics, Beijing Tongren Hospital, Capital Medical University from October 2013 to December 2019.The clinical features and the high risk factors were analyzed by using SPSS 21.0 software.Results:(1)The median age at diagnosis was 0.13 years (0 to 4.92 years), predominantly in males(14/16 cases, 87.5%). (2)Focus site: 10 cases were located in the extremities, 3 cases in the head and neck, and 3 cases in the trunk.(3)Treatment plan was mainly surgical combined chemotherapy.The initial treatment was " Vincristine + Cyclophosphamide + Actinomycin D" . Among the 15 cases receiving chemotherapy, 3 cases were insensitive to chemotherapy and 12 cases were sensitive to chemotherapy.There were 14 cases of tumor resection and 2 cases of biopsy.(4) The median follow-up time was 3.5 years, and 3 patients′ parents gave up the treatment due to the progress of the disease after chemotherapy and died.The remaining 13 cases were completely relieved until the follow-up period, of which 2 cases relapsed (2/16 cases, 12.5%) and the overall 5-year survival rate was about 70%.Grouped by pathological grade, the total 5-year survival rate of children with G1 and G2 was 100%, and G3 was only 30%, with statistically significant differences ( χ2=4.853, P=0.028). Conclusions:The overall prognosis of IFS is favorable.Tumor grade and lesion size are important factors that affect the prognosis.Adjuvant chemotherapy is beneficial to complete tumor resection, and chemotherapy is recommended for children with high risk factors.

Fibrosarcoma infantil intestinal. Reporte de un caso con sangrado digestivo en un lactante / Infantile intestinal fibrosarcoma. Case report with digestive bleeding in an infant

El fibrosarcoma infantil es un tumor raro, perteneciente al grupo de sarcomas no rabdomiosarcoma; se presenta, preferentemente, en infantes, con localización más frecuente en extremidades.Se reporta un varón de 5 meses, con historia de sangrado digestivo desde los 3 meses, interpretados, al principio, como alergia a la proteína de leche de vaca, con evolución tórpida y anemia. Por laparoscopía exploradora, se evidenció un tumor en el intestino medio; se realizó resección y anastomosis término-terminal. Luego, se ampliaron los márgenes de resección por ser < 0,1 cm.Microscópicamente, se observó una proliferación neoplásica fusocelular con positividad difusa para vimentina, y reacción en cadena de la polimerasa con transcriptasa reversa positiva para ETV6-NTRK3. Se diagnosticó fibrosarcoma infantil intestinal. Presentó buena evolución a 24 meses del diagnóstico. Si bien es infrecuente en pediatría, se debe considerar como diagnóstico diferencial en lactantes con sangrado digestivo sin causa clara.

Infantile fibrosarcoma is a rare tumor, belonging to the non-rhabdomyosarcoma, soft tissue sarcoma. It is mostly presented in infants, most commonly involving the extremities.We report a 5-month-old boy, presenting with digestive bleeding since the age of 3 months, initially diagnosed as cow's milk allergy, with a torpid evolution and anemia. He underwent laparoscopic exploration, with evidence of a mass in the small bowel. Resection and end-to-end anastomosis were performed. Because of inadequate microscopic margins (< 1 cm), a new surgery was performed to achieve tumor free margins. Histological examination consisted of spindle cells that mainly expressed vimentin, and reverse transcriptase-polymerase chain reaction was positive for the ETV6-NTRK3 transcript, confirming the diagnosis of infantile fibrosarcoma. The patient did well after 24 months of follow-up.Although infantile intestinal fibrosarcoma is extremely uncommon in children, it should be considered as differential diagnosis for digestive bleeding in infants

Neoplasms in domestic hamsters in Southern Brazil: epidemiological and pathological aspects of 40 cases1 / Neoplasias em hamsters domésticos no Sul do Brasil: aspectos epidemiológicos e patológicos de 40 casos

Although neoplasms are commonly reported in domestic hamsters, retrospective studies approaching spontaneous tumors with data regarding epidemiological findings are scarce. The present study aimed to describe the epidemiological and pathological findings of 40 cases of tumors in domestic hamsters diagnosed in a veterinary pathology laboratory in Southern Brazil from 2002 to 2019. Chinese hamster (Cricetulus griseus) was the most commonly affected species (16/40), followed by Djungarian hamster (Phodopus sungorus, 11/40) and Syrian hamster (Mesocricetus auratus, 4/40). Among the cases, 57.5% were females (23/40), while 42.5% were males (17/40). The affected hamsters' median age was of 14-months old, with an age range of 8- to 36-months old. Twenty-four cases were assessed as anatomopathological samples (biopsies), while 16 were composed of carcasses submitted to postmortem examination, and, therefore, the neoplasm was related to the cause of death. The integumentary system was frequently affected (60%, 24/40), followed by the female reproductive tract (22.5%, 9/40), hematopoietic system (10%, 4/40), digestive tract (5%, 2/40), and endocrine system (2.5%, 1/40). The most frequent neoplasm was squamous cell carcinoma (35%, 14/40), mostly on the lip/nasal region (50%, 7/14). Other tumors included fibrosarcoma (10%, 4/40), lymphoma (10%, 4/40), mammary cystadenoma (10%, 4/40), apocrine sweat gland adenoma (7.5%, 3/40), hemangiosarcoma (5%, 2/40), leiomyosarcoma (5%, 2/40), and granulosa ovarian cell tumor (5%, 2/40). The five remaining cases occurred individually and were composed of hepatoid gland adenoma, solid thyroid carcinoma, cutaneous melanoma, ovarian teratoma, and cutaneous trichoblastoma. Neoplasms were identified as an important cause of death and major reason to perform biopsy in domestic hamsters in Southern Brazil.(AU)

Embora neoplasmas em hamsters domésticos sejam comumente relatados, estudos retrospectivos abordando neoplasias espontâneas e os dados epidemiológicos associados são escassos. O presente estudo teve o objetivo de descrever os principais achados epidemiológicos e patológicos de 40 casos de tumores em hamsters domésticos diagnosticados em um laboratório de patologia veterinária do Sul do Brasil de 2002 a 2019. A principal espécie acometida foi o hamster chinês (Cricetulus griseus, 16/40), seguido por hamster anão russo siberiano (Phodopus sungorus, 11/40) e hamster sírio (Mesocricetus auratus, 4/40). As fêmeas corresponderam a 57,5% dos casos (23/40), enquanto os machos representaram 42,5% (17/40). Foram afetados roedores com uma faixa etária de 8 a 36 meses de idade, e uma mediana de 14 meses. Do total de casos, 24 foram exames anatomopatológicos (biopsias) e 16 casos foram examinados através de necropsia e, portanto, relacionados com a causa da morte dos animais. O sistema tegumentar foi o mais frequentemente acometido (60%; 24/40), seguido pelo trato reprodutivo (22,5%; 9/40), sistema hematopoietico (10%; 4/40), trato digestório (5%; 2/40) e sistema endócrino (2,5%; 1/40). A neoplasia mais frequentemente diagnosticada foi o carcinoma de células escamosas (35%; 14/40), localizado principalmente em região labionasal (50%; 7/14). Outros tumores incluíram fibrossarcoma (10%; 4/40), linfoma (10%; 4/40), adenoma cístico de glândula mamária (10%; 4/40), adenoma de glândula sudorípara (7,5%; 3/40), hemangiossarcoma (5%; 2/40), leiomiossarcoma (5%; 2/40) e tumor de células da granulosa (5%; 2/40). Os outros cinco casos remanescentes ocorreram individualmente e eram compostos por adenoma de glândula hepatoide, carcinoma sólido de tireoide, melanoma cutâneo, teratoma ovariano e tricoblastoma cutâneo. Neoplasmas foram identificados como importantes causas de morte ou razões para realização de biopsia em hamsters domésticos no Sul do Brasil.(AU)

Large anterior abdominal wall fibrosarcoma in a known case of recurrent dermatofibrosarcoma protuberans

Dermatofibrosarcoma protuberans is a rare soft tissue sarcoma of low to intermediate malignant potential. Incidence is estimated to be 0.8 to 4.5 cases per million persons per year. The tumor is highly aggressive locally and is known to recur. Punch biopsy or excisional biopsy (in case of small tumors) are diagnostic. Computer tomography (CT) and magnetic resonance imaging (MRI) are useful in determining the size and extent of the tumor’s treatment is primarily surgical, with a wide local excision with at 2 cm margin. However, local recurrence after apparently adequate surgical excision is common. Mohs micrographic surgery has been recommended as it enables maximum preservation of tissue. When surgery is insufficient, imatinib mesylate is shown as a safe and effective treatment in dermatofibrosarcoma protuberans (DFSP), especially in cases of locally advanced or metastatic disease. Here, we report a case of a giant fibrosarcoma on the anterior abdominal wall, measuring 27×18×9 cm, which occurred in a recurrent dermatofibrosarcoma protuberans. Diagnosis was done by histopathological examination (HPE) of the previously excised tumor and CT was done. The tumor was excised with a 3 cm margin and extensive reconstruction of the anterior abdominal wall defect was done using synthetic mesh, myocutaneous flaps and split skin grafting. Keeping in view the recurrent nature of our case, large tumor size, DFSP-fibrosarcomatous (FS) transformation and close negative margins in the HPE of the postoperative specimen, the patient was planned for adjuvant radiotherapy.

RECK and TIMP-2 mediate inhibition of MMP-2 and MMP-9 by Annona muricata

Up-regulation of MMP-2 and MMP-9 plays a significant role in promoting cancer progression by degradingthe components of the extracellular matrix, thereby enhancing the migration of tumor cells. Although the antiproliferative and apoptotic effect of Annona muricata is well established, its effect on MMP-2 and MMP-9, amajor target in several types of cancers, has not been studied. Powdered samples of various parts of A.muricata like fruit, stem, seed, and twig extracted using aqueous methanol showed significant dose-dependentinhibition of MMP-2 and MMP-9 in a highly metastatic fibrosarcoma cell line, HT1080. Additionally, theseextracts also up-regulated the expression of several endogenous inhibitors of MMP-2 and MMP-9 likeREversion-inducing Cysteine-rich protein with Kazal motifs (RECK) and Tissue Inhibitor of Metalloproteinase-2 (TIMP-2). Furthermore, primary cells developed from tumor tissues obtained from patients notexposed to chemotherapy, also exhibited similar results. Remarkably, the inhibition of MMP-2 and MMP-9observed was tumor specific, with the A. muricata fruit extract showing only 2% inhibition in cells obtainedfrom normal tissues, when compared to 60% inhibition observed in cells obtained from tumor samples. Thepresent study elucidates a novel mechanism by which A. muricata extracts selectively exhibit their anti-canceractivity in tumor cells by down-regulating MMP-2 and MMP-9 that are important biomarkers in cancer.

Glucagon-like peptide-1 and gastrin synergistically promote the differentiation of insulin-producing cells / 中华内分泌代谢杂志

Objective@#Glucagon-like peptide-1(GLP-1) and gastrin synergistically promote the differentiation of insulin-producing cells which differentiated from rat bone marrow mesenchymal stem cells (BMSCs).@*Methods@#(1)Prepare IPCs model: pancreatic duodenal homeobox 1 (Pdx-1), neurogenin 3 (Ngn3) combined with V-type tendon fibrosarcoma oncogene homolog A (MafA) co-transfected BMSCs differentiation into IPCs; (2)IPCs were divided into 4 groups: Group A(uninduced group), group B(GLP-1 induction group), group C(gastrin induction group), and group D(GLP-1 combined with gastrin induction group). Cultured in high glucose medium for 7 days, the expression levels of insulin2, Pdx-1, GK, nestin, and glucagon mRNA were detected by RT-PCR. The insulin secretion of each group was detected by ELISA.@*Results@#After cultured for 7 days under high glucose conditions, the morphology of IPCs in each induction group changed significantly, gradually aggregated and formed scattered cell masses, and the combined induction group formed large cell masses. The staining of disulfide brown was reddish brown; The levels of insulin secretion increased gradually on the 0, 3rd, 5th, 7th, and 9th day after induction, and the increase was the most significant in the combined induction group (P<0.05). Compared with group A, the expression of insulin2 and GK in group B and D was significantly up-regulated, the expression of glucagon was down-regulated in group D, the expression of Pdx-1 was down-regulated in group C, and the expression of glucagon was up-regulated (P<0.05). Compared with group B, The expression of insulin2 was down-regulated in group C, and the expression level of glucagon was up-regulated. The expression levels of Pdx-1 and Insulin2 were significantly up-regulated in group D, and the expression level of glucagon was down-regulated (P<0.05). Compared with group C, the expression level of Pdx-1, insulin2 and GK was significantly up-regulated in group D, and the expression level of glucagon was down-regulated (P<0.05).@*Conclusion@#GLP-1 and gastrin synergistically promote the differentiation of IPCs into islet β cells by up-regulating GK and insulin2 and down-regulating glucagon.

Fibrosarcoma congénito de rodilla. Reporte de caso / Congenital fibrosarcoma of the knee. Case report

El fibrosarcoma congénito, es una patología muy poco habitual, que representa el 3% de todos los tumores de la infancia. El propósito de la publicación es describir el caso clínico de una paciente con un fibrosarcoma congénito tratado exitosamente quirúrgicamente sin recurrencias con buenos resultados funcionales. Se presenta una caso de una paciente a quien se le diagnostico a los 3 meses de edad una masa en el muslo izquierdo por un fibrosarcoma congénito de 10cm de diámetro, a quien se le realizo resección primaria de la lesión con bordes libre de compromiso tumoral como tratamiento de elección. En el seguimiento, la paciente no ha presentado recaídas con recuperación de los arcos de movilidad activa y pasiva, con desarrollo motor acorde a la edad. Los fibrosarcomas congénitos, se ubican principalmente alrededor de la rodilla, y son infiltrantes a tejidos adyacentes, su elección de manejo es la resección quirúrgica con bordes libres de tumor, en general tiene un mejor pronóstico que los sarcomas en adultos, pero con índices de recurrencia de hasta el 40% de los casos. Nivel de evidencia: IV

Congenital fibrosarcoma is an unusual pathology, representing 3% of all childhood tumors. The purpose of the publication is to describe the clinical case of a patient with a congenital fibrosarcoma, successfully treated surgically without recurrences with good functional results. We describe the clinical outcome of a 3-month-old of age with a mass in the left thigh by a congenital fibrosarcoma 10cm, who underwent primary resection of the lesion with edges free of tumor compromise as the treatment of choice. During follow-up, the patient did not present relapses with recovery of active and passive mobility arcs, with motor development according to age. The congenital fibrosarcomas, are located mainly around the knee, and are infiltrating to adjacent tissues; management is surgical resection with tumor-free edges. Congenital Fibrosarcoma usually has better prognosis than adults sarcomas, but with recurrence rates up to 40% of the patients. Evidence Level: IV

Cervical Infantile Fibrosarcoma: a rare cause of paediatric parapharyngeal neck mass

Soft tissue tumors are not uncommon in childhood and comprise entities that range from common to very rare malignancies. Infantile fibrosarcoma (IFS) is a rare pediatric malignancy mainly seen in the first two years of life. The data about the incidence of infantile fibrosarcoma occurring in the neck in the Indian subcontinent is scarce. To the best of our knowledge, only one case of infant cervical IFS has been reported previously in the Indian subcontinent. We present another case of an eight-year-old male patient with a rapidly growing mass on the left side of the neck. He was successfully treated with a combined modality of surgery and chemotherapy with a good outcome. Among the soft tissue tumors of childhood, IFS is a rare entity. It has a good prognosis and lesser chance of distant metastasis as compared to adult fibrosarcoma. Though surgical excision is the mainstay of treatment, chemotherapy also has a significant role in the treatment of primary tumor and metastasis. We discuss the stated case to bring to the notice this uncommon cause, which can be considered as a differential diagnosis of upper cervical swellings. A better understanding of this entity would help in early diagnosis and aggressive treatment, reducing the overall morbidity and mortality.

Fibrosarcoma of the Oral Cavity: A Case Report

Fibrosarcomas are relatively uncommon malignant tumors arising from fibrous connective tissue and are characterized by increased abnormal proliferation of malignant fibroblast. Fibrosarcoma is capable of local recurrence and metastasis with poor prognosis. Approximately 0.05% of cases are noted in the head and neck region amongst all the cases recorded in the human race. In the present case, we report a case of fibrosarcoma of the mandible in 24 years old female who was presented with small intraoral swelling in the lower anterior vestibule with the involvement of floor of the mouth. Histopathology revealed a proliferation of malignant fibroblast cells arranged in a classical herringbone pattern.

The performance of ultrasound for differentiation of infantile fibrosarcoma and soft tissue hemangioma / 中华超声影像学杂志

Objective@#To investigate the differential performance of ultrasound between infantile fibrosarcoma(IFS) and soft tissue hemangioma.@*Methods@#The retrospective study was conducted from January 2012 to January 2019 in Beijing Children′s Hospital, Capital Medical University. A total of 16 patients with IFS were consecutively collected as IFS group, and 26 consecutive patients with soft tissue hemangioma (hemangioma group) were selected for comparison according to the tumor size of IFS. All the final diagnosis got confirmed by pathological analysis. The ultrasonographic features of IFS and hemangioma were compared and analyzed, and after weighting on the basis of the dominance ration (OR), the ultrasonic features with diagnostic value were used to establish the prediction equation. Then, the differential performance of every feature and the prediction equation was evaluated via the ROC analysis.@*Results@#There were differences in the lesion echo, margin and blood flow characteristics between IFS group and hemangioma group (P=0.013, 0.002, 0.005), the area under the ROC (AUC) of applying every ultrasonic feature with diagnostic value for differentiation were 0.695, 0.740, and 0.700, respectively. Benefiting from the employment of the prediction equation, the AUC was improved to 0.887 with a sensitivity of 81.3% and a specificity of 96.2%, which were better than the diagnosis by any single feature (P=0.017, 0.035, 0.003).@*Conclusions@#Ultrasound can be utilized to discriminate infantile fibrosarcoma from soft tissue hemangioma. The use of prediction equation can further improve the differential performance with higher clinical value.

The performance of ultrasound for differentiation of infantile fibrosarcoma and soft tissue hemangioma / 中华超声影像学杂志

Objective To investigate the differential performance of ultrasound between infantile fibrosarcoma(IFS) and soft tissue hemangioma.Methods The retrospective study was conducted from January 2012 to January 2019 in Beijing Children's Hospital,Capital Medical University.A total of 16 patients with IFS were consecutively collected as IFS group,and 26 consecutive patients with soft tissue hemangioma (hemangioma group) were selected for comparison according to the tumor size of IFS.All the final diagnosis got confirmed by pathological analysis.The ultrasonographic features of IFS and hemangioma were compared and analyzed,and after weighting on the basis of the dominance ration (OR),the ultrasonic features with diagnostic value were used to establish the prediction equation.Then,the differential performance of every feature and the prediction equation was evaluated via the ROC analysis.Results There were differences in the lesion echo,margin and blood flow characteristics between IFS group and hemangioma group (P =0.013,0.002,0.005),the area under the ROC (AUC) of applying every ultrasonic feature with diagnostic value for differentiation were 0.695,0.740,and 0.700,respectively.Benefiting from the employment of the prediction equation,the AUC was improved to 0.887 with a sensitivity of 81.3 ％ and a specificity of 96.2 ％,which were better than the diagnosis by any single feature (P =0.017,0.035,0.003).Conclusions Ultrasound can be utilized to discriminate infantile fibrosarcoma from soft tissue hemangioma.The use of prediction equation can further improve the differential performance with higher clinical value.

Clinicopathological analysis of infantile/congenital fibrosarcomas with rare histological features / 中华病理学杂志

Objective@#To analyze the clinicopathological features, immunohistochemical (IHC) phentotype,diagnosis and differential diagnosis of infantile/congenital fibrosarcoma (IFS/CFS) with unusual histological features.@*Methods@#Five IFS/CFS at Children′s Hospital of Fudan University from March 2014 to July 2018 were analyzed for their diagnosis and differential diagnosis.@*Results@#Two cases were males, three cases were females. The clinical manifestation of IFS/CFS was a rapidly-growing and painless mass. There were no specific radiologic features. Histologically, the tumor cells are arranged in intersecting or sheet-like patterns. There were focal hemangioma-like areas in four cases. There were also focal areas of primitive asteroid, short-spindled, and oval tumor cells in three cases. IHC study showed the tumor cells diffusely expressed TLE1(2/5), Vimentin(5/5), and WT1(3/5), in a cytoplastic pattern; they focally expressed CD34(3/5), CD31(3/5), and α-SMA(2/5). Fluorescence in situ hybridization (FISH) detected break-apart positivity of ETV6 gene.@*Conclusions@#Hemangioma-like pattern, myxoid area, and TLE1 expression is very rare in IFS/CFS. Detection of ETV6 gene break-apart by FISH is very helpful in the diagnosis and differential diagnosis of IFS/CFS.

Tumor desmoide / Desmoid tumor

Introducción. El tumor desmoide grado I, es una patología rara, se consideraba la intervención quirúrgica como primera opción, pero su recidiva posquirúrgica tendía a obscurecer la evolución satisfactoria ya que este tipo de tumores tienden a comprometer planos cada vez más profundos, en algunos casos ha provocado la amputación de extremidades sin lograr éxito, generando un grave impacto psicológico en el paciente y su pronóstico. Caso clínico. Paciente masculino, a los 18 años de edad, presentó una masa en el tercio distal del brazo izquierdo, en Italia le realizan exéresis quirúrgica, la misma que reporta positivo para tumor desmoide, presentando varias recidivas años después, estudios histopatológicos reportan recidiva de tumor desmoide. Actualmente se encuentra en seguimiento con controles tomográficos. Discusión. El tumor desmoide carece de potencial metastásico, con un comportamiento local muy agresivo, las técnicas de imagen permiten realizar su diagnóstico diferencial de otros tumores que afectan los tejidos blandos, su diagnóstico definitivo es con biopsia y su estudio histopatológico. Nuestro paciente a los 18 años se le diagnostica de un tumor desmoide a nivel del brazo izquierdo, presentando por varias ocasiones recidivas posterior a varias exéresis de los mismos, cabe recalcar, que este tipo de tumor tiene una elevada tasa de recurrencia incluso después de una resección completa del tumor; por lo que la cirugía no está indicada como tratamiento de primera elección, indica el manejo expectante está indicado con la estrategia O-E (Observar-Esperar), cuando el paciente es referido al HECAM se decide mantener controles expectantes. Como lo recomienda las ultimas guías de tratmiento.

Introduction. Grade I desmoid tumor is an uncommon pathology where treatment was the surgery as first option, but its post-surgical recurrence tends to obscure satisfactory evolution due to these kinds of tumors have to compromise deep layers, and there are cases where patients needed amputation of their arms or legs without any success; therefore, it causes a huge psychological impact in the patients and their prognosis. Clinical case. An eighteen-year old male presented with a mass in the distal portion of the left arm. In Italy, he had a surgical resection, and the sample was positive for a desmoid tumor, presenting several recurrences years later. Histological studies reports recurrence of desmoid tumor. Is currently in follow-up with tomographic controls. Discussion. The desmoid tumor lacks metastatic potential, with a very aggressive local behavior, the imaging techniques allow its differential diagnosis of other tumors that affect the soft tissues, and its definitive diagnosis is with biopsy and its histopathological study. In summary, our eighteen-year old patient's diagnose was a desmoid tumor on his left arm, presenting several recurrences after several exeresis of the same, it should be emphasized that this type of tumor has a high rate of recurrence even after a complete tumor resection. Thus, surgery is not indicated as first-line of treatment, so it´s recommended expectant treatment based on the O-E strategy (Observe-Wait). When the patient was referred to Hospital de Especialidades Carlos Andrade Marin, the doctors decided to continue with observational management. As recommended by the latest treatment guidelines.